The objective of the proposed study is to characterize the pathophysiological alterations induced by IgE antibody in respiratory and circulatory structure and/or function and to elucidate the mechanisms by which such alterations occur. The experimental design involves the utilization of a unique model system in which rabbits sensitized to either horseradish peroxidase or TNP-bovine serum albumin synthesize only IgE antibody to that antigen and upon intravenous challenge exhibit systemic anaphylaxis. This systemic allergic reaction has been characterized with respect to alterations in 8 variables in respiratory and circulatory function: breathing frequency, tidal volume, minute ventilation, total pulmonary resistance, dynamic compliance, heart rate, pulmonary artery pressure and aortic pressure. We propose to examine the acute allergic reaction to determine (a) whether IgE and antigen are the only essential components for initiation in an otherwise normal animal; (b) whether basophils or mast cells or both play a role in the response; (c) whether platelets are a requirement of the reponse; and (d) whether the response can be prevented by inhibiting the effects of specific substances though to mediate acute allergic reactions. We also propose to directly demonstrate the site of IgE-induced airway alteration(s) through the use of a new radiological tool--the microfocal spot technique. We will perform these studies by determining the effects of specific interventions or chemical agents on the 8 physiological variables given above, using the alterations established previously for the acute allergic reaction as a basis for comparison. We will compare this acute reaction on to that in sensitized rabbits repeadly challenged with antigen over a peiod of 12 months in order to identify any role for IgE in inducing chronic alterations. We will also compare the response to aerosol vs intravenously administered antigen in order to detemine the site of antigen-IgE interaction and any circulatory alterations which occur in response to aerosol challenge.